Antibody mimetic

Antibody mimetics are organic compounds that, like antibodies, can specifically bind antigens, but that are not structurally related to antibodies. They are usually artificial peptides or proteins with a molar mass of about 3 to 20 kDa. Nucleic acids and small molecules are sometimes considered antibody mimetics as well, but not artificial antibodies, antibody fragments and fusion proteins composed from these. Some types have an antibody-like beta-sheet structure. Common advantages over antibodies are better solubility, tissue penetration, stability towards heat and enzymes, and comparatively low production costs. Antibody mimetics are being developed as therapeutic and diagnostic agents.[1]

Examples

Antibody mimetic Scaffold Molar mass Example drug
Affibody molecules[2] Z domain of Protein A 6 kDa ABY-025
Affilins[3] Gamma-B crystallin 20 kDa
Ubiquitin 10 kDa SPVF 2801
Affitins[4] Sac7d (from Sulfolobus acidocaldarius) 7 kDa
Anticalins[5] Lipocalins 20 kDa
Avimers[6] A domains of various membrane receptors 9–18 kDa
DARPins[7] Ankyrin repeat motif 10–19 kDa MP0112
Fynomers[8] SH3 domain of Fyn 7 kDa
Kunitz domain peptides[9] Kunitz domains of various protease inhibitors 6 kDa Ecallantide
Monobodies[10] 10th type III domain of fibronectin 10 kDa Angiocept

References

  1. ^ Gebauer M, Skerra A (June 2009). "Engineered protein scaffolds as next-generation antibody therapeutics". Curr Opin Chem Biol 13 (3): 245–255. doi:10.1016/j.cbpa.2009.04.627. PMID 19501012. http://linkinghub.elsevier.com/retrieve/pii/S1367-5931(09)00068-4. 
  2. ^ Nygren PA (June 2008). "Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle scaffold". FEBS J. 275 (11): 2668–76. doi:10.1111/j.1742-4658.2008.06438.x. PMID 18435759. 
  3. ^ Ebersbach H, Fiedler E, Scheuermann T, et al. (September 2007). "Affilin-novel binding molecules based on human gamma-B-crystallin, an all beta-sheet protein". J. Mol. Biol. 372 (1): 172–85. doi:10.1016/j.jmb.2007.06.045. PMID 17628592. 
  4. ^ Krehenbrink M, Chami M, Guilvout I, Alzari PM, Pécorari F, Pugsley AP (November 2008). "Artificial binding proteins (Affitins) as probes for conformational changes in secretin PulD". J. Mol. Biol. 383 (5): 1058–68. doi:10.1016/j.jmb.2008.09.016. PMID 18822295. http://linkinghub.elsevier.com/retrieve/pii/S0022-2836(08)01117-0. 
  5. ^ Skerra A (June 2008). "Alternative binding proteins: anticalins - harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities". FEBS J. 275 (11): 2677–83. doi:10.1111/j.1742-4658.2008.06439.x. PMID 18435758. 
  6. ^ Silverman J, Liu Q, Lu Q, et al. (December 2005). "Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains". Nat. Biotechnol. 23 (12): 1556–61. doi:10.1038/nbt1166. PMID 16299519. 
  7. ^ Stumpp MT, Binz HK, Amstutz P (August 2008). "DARPins: a new generation of protein therapeutics". Drug Discov. Today 13 (15–16): 695–701. doi:10.1016/j.drudis.2008.04.013. PMID 18621567. http://linkinghub.elsevier.com/retrieve/pii/S1359-6446(08)00162-1. 
  8. ^ Grabulovski D; Kaspar, M; Neri, D (2007). "A novel, non-immunogenic Fyn SH3-derived binding protein with tumor vascular targeting properties". J Biol Chem 282 (5): 3196–3204. doi:10.1074/jbc.M609211200. PMID 17130124. 
  9. ^ Nixon AE, Wood CR (March 2006). "Engineered protein inhibitors of proteases". Curr Opin Drug Discov Devel 9 (2): 261–8. PMID 16566296. 
  10. ^ Koide A, Koide S (2007). "Monobodies: antibody mimics based on the scaffold of the fibronectin type III domain". Methods Mol. Biol. 352: 95–109. PMID 17041261. 
Engineered monoclonal antibodies and antibody mimetics
Whole antibody
Fab fragment
Variable fragment
Smaller units
Intracellular
Antibody mimetics